Analysis of clonality and antibiotic resistance among early clinical isolates of Enterococcus faecium in the United States.

BACKGROUND: The Enterococcus faecium genogroup, referred to as clonal complex 17 (CC17), seems to possess multiple determinants that increase its ability to survive and cause disease in nosocomial environments. METHODS: Using 53 clinical and geographically diverse US E. faecium isolates dating from 1971 to 1994, we determined the multilocus sequence type; the presence of 16 putative virulence genes (hyl(Efm), esp(Efm), and fms genes); resistance to ampicillin (AMP) and vancomycin (VAN); and high-level resistance to gentamicin and streptomycin. RESULTS: Overall, 16 different sequence types (STs), mostly CC17 isolates, were identified in 9 different regions of the United States. The earliest CC17 isolates were part of an outbreak that occurred in 1982 in Richmond, Virginia. The characteristics of CC17 isolates included increases in resistance to AMP, the presence of hyl(Efm) and esp(Efm), emergence of resistance to VAN, and the presence of at least 13 of 14 fms genes. Eight of 41 of the early isolates with resistance to AMP, however, were not in CC17. CONCLUSIONS: Although not all early US AMP isolates were clonally related, E. faecium CC17 isolates have been circulating in the United States since at least 1982 and appear to have progressively acquired additional virulence and antibiotic resistance determinants, perhaps explaining the recent success of this species in the hospital environment.

Continuum of depressive and manic mixed states in patients with bipolar disorder: quantitative measurement and clinical features.

Bipolar mixed states combine depressive and manic features, presenting diagnostic and treatment challenges and reflecting a severe form of the illness. DSM-IV criteria for a mixed state require combined depressive and manic syndromes, but a range of mixed states has been described clinically. A unified definition of mixed states would be valuable in understanding their diagnosis, mechanism and treatment implications. We investigated the manner in which depressive and manic features combine to produce a continuum of mixed states. In 88 subjects with bipolar disorder (DSM-IV), we evaluated symptoms and clinical characteristics, and compared depression-based, mania-based, and other published definitions of mixed states. We developed an index of the extent to which symptoms were mixed (Mixed State Index, MSI) and characterized its relationship to clinical state. Predominately manic and depressive mixed states using criteria from recent literature, as well as Kraepelinian mixed states, had similar symptoms and MSI scores. Anxiety correlated significantly with depression scores in manic subjects and with mania scores in depressed subjects. Discriminant function analysis associated mixed states with symptoms of hyperactivity and negative cognitions, but not subjective depressive or elevated mood. High MSI scores were associated with severe course of illness. For depressive or manic episodes, characteristics of mixed states emerged with two symptoms of the opposite polarity. This was a cross-sectional study. Mixed states appear to be a continuum. An index of the degree to which depressive and manic symptoms combine appears useful in identifying and characterizing mixed states. We propose a depressive or manic episode with three or more symptoms of the opposite polarity as a parsimonious definition of a mixed state.

Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. RESULTS: Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. CONCLUSION: Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.

Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates.

Crystal structures of progressive Ca2+ binding states of the Ca2+ sensor Ca2+ binding domain 1 (CBD1) from the CALX Na+/Ca2+ exchanger reveal incremental conformational transitions.

Na(+)/Ca(2+) exchangers (NCX) constitute a major Ca(2+) export system that facilitates the re-establishment of cytosolic Ca(2+) levels in many tissues. Ca(2+) interactions at its Ca(2+) binding domains (CBD1 and CBD2) are essential for the allosteric regulation of Na(+)/Ca(2+) exchange activity. The structure of the Ca(2+)-bound form of CBD1, the primary Ca(2+) sensor from canine NCX1, but not the Ca(2+)-free form, has been reported, although the molecular mechanism of Ca(2+) regulation remains unclear. Here, we report crystal structures for three distinct Ca(2+) binding states of CBD1 from CALX, a Na(+)/Ca(2+) exchanger found in Drosophila sensory neurons. The fully Ca(2+)-bound CALX-CBD1 structure shows that four Ca(2+) atoms bind at identical Ca(2+) binding sites as those found in NCX1 and that the partial Ca(2+) occupancy and apoform structures exhibit progressive conformational transitions, indicating incremental regulation of CALX exchange by successive Ca(2+) binding at CBD1. The structures also predict that the primary Ca(2+) pair plays the main role in triggering functional conformational changes. Confirming this prediction, mutagenesis of Glu(455), which coordinates the primary Ca(2+) pair, produces dramatic reductions of the regulatory Ca(2+) affinity for exchange current, whereas mutagenesis of Glu(520), which coordinates the secondary Ca(2+) pair, has much smaller effects. Furthermore, our structures indicate that Ca(2+) binding only enhances the stability of the Ca(2+) binding site of CBD1 near the hinge region while the overall structure of CBD1 remains largely unaffected, implying that the Ca(2+) regulatory function of CBD1, and possibly that for the entire NCX family, is mediated through domain interactions between CBD1 and the adjacent CBD2 at this hinge.

Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.

Adolescents’ Sexual Health Matters: Texas Should Get on Board

Texas has an appalling record on adolescent sexual health. The Markham, et al. analysis of three data sets comparing Texas with the United States suggests what can be done to remedy the state's negative trends: (1) acknowledge that teens are having sex; (2) provide earlier, medically-accurate sex education; and, (3) provide reproductive health services in school-based health centers.

Commentary on "A Tale of Two States"

While both California and Texas have experienced declines in teen birth rates over the past three decades, declines in California have been larger, particularly among Hispanic teens. Differences in state policies may have shaped this disparity, as suggested by Tortolero and her colleagues in their article “A Tale of Two States: What We Learn from California and Texas”. Fundamental differences exist between Texas and California in their approaches to sex education, access to family planning services for teens, and public-private partnerships. However, methodological challenges are present when drawing state comparisons, including the limitations of available public health data and the difficulty of disaggregating state characteristics from state policies. Based on their comparison of state data and policies, Tortolero and her colleagues issue sensible recommendations for reducing the teen birth rate in Texas. History suggests that state policies are most effective when political commitment is linked to scientifically effective approaches. Based on our understanding of the scientific literature, the most effective strategies for reducing rates of teen childbearing in Texas would be providing comprehensive school sexuality education and improving teen access to contraceptive services.

A Tale of Two States: What We Learn from California and Texas

Teen birth rates and teen pregnancy prevention strategies vary widely across individual states in the US, which has the highest overall teen birth rate among developed nations. California and Texas, the two most populous states currently accounting for a quarter of all teen births, have taken very different approaches to addressing adolescent reproductive health. This case study examines the racial/ethnic composition and socioeconomic factors of these two states from 1981 to 2008. State programs and policies implemented between 1991 and 2008 as well as changes in access to contraception and public–private partnerships are discussed. Based on the lessons learned from California, a similar multifaceted campaign in Texas may be effective in reducing teen births.

A prospective cohort study evaluating the state of medical readiness in the United States Air Force and risk factors to improve the medical readiness posture

A cohort of 418 United States Air Force (USAF) personnel from over 15 different bases deployed to Morocco in 1994. This was the first study of its kind and was designed with two primary goals: to determine if the USAF was medically prepared to deploy with its changing mission in the new world order, and to evaluate factors that might improve or degrade USAF medical readiness. The mean length of deployment was 21 days. The cohort was 95% male, 86% enlisted, 65% married, and 78% white.^ This study shows major deficiencies indicating the USAF medical readiness posture has not fully responded to meet its new mission requirements. Lack of required logistical items (e.g., mosquito nets, rainboots, DEET insecticide cream, etc.) revealed a low state of preparedness. The most notable deficiency was that 82.5% (95% CI = 78.4, 85.9) did not have permethrin pretreated mosquito nets and 81.0% (95% CI = 76.8, 84.6) lacked mosquito net poles. Additionally, 18% were deficient on vaccinations and 36% had not received a tuberculin skin test. Excluding injections, the overall compliance for preventive medicine requirements had a mean frequency of only 50.6% (95% CI = 45.36, 55.90).^ Several factors had a positive impact on compliance with logistical requirements. The most prominent was "receiving a medical intelligence briefing" from the USAF Public Health. After adjustment for mobility and age, individuals who underwent a briefing were 17.2 (95% CI = 4.37, 67.99) times more likely to have received an immunoglobulin shot and 4.2 (95% CI = 1.84, 9.45) times more likely to start their antimalarial prophylaxsis at the proper time. "Personnel on mobility" had the second strongest positive effect on medical readiness. When mobility and briefing were included in models, "personnel on mobility" were 2.6 (95% CI = 1.19, 5.53) times as likely to have DEET insecticide and 2.2 (95% CI = 1.16, 4.16) times as likely to have had a TB skin test.^ Five recommendations to improve the medical readiness of the USAF were outlined: upgrade base level logistical support, improve medical intelligence messages, include medical requirements on travel orders, place more personnel on mobility or only deploy personnel on mobility, and conduct research dedicated to capitalize on the powerful effect from predeployment briefings.^ Since this is the first study of its kind, more studies should be performed in different geographic theaters to assess medical readiness and establish acceptable compliance levels for the USAF. ^

Patterns of alcohol and illicit substance use in the United States and Mexico. Substantive and methodologic issues in the cross-national analysis of alcohol and drug use data

This research examines prevalence of alcohol and illicit substance use in the United States and Mexico and associated socio-demographic characteristics. The sources of data for this study are public domain data from the U.S. National Household Survey of Drug Abuse, 1988 (n = 8814), and the Mexican National Survey of Addictions, 1988 (n = 12,579). In addition, this study discusses methodologic issues in cross-cultural and cross-national comparison of behavioral and epidemiologic data from population-based samples. The extent to which patterns of substance abuse vary among subgroups of the U.S. and Mexican populations is assessed, as well as the comparability and equivalence of measures of alcohol and drug use in these national samples.^ The prevalence of alcohol use was somewhat similar in the two countries for all three measures of use: lifetime, past year and past year heavy use, (85.0%, 68.1%, 39.6% and 72.6%, 47.7% and 45.8% for the U.S. and Mexico respectively). The use of illegal substances varied widely between countries, with U.S. respondents reporting significantly higher levels of use than their Mexican counterparts. For example, reported use of any illicit substance in lifetime and past year was 34.2%, 11.6 for the U.S., and 3.3% and 0.6% for Mexico. Despite these differences in prevalence, two demographic characteristics, gender and age, were important correlates of use in both countries. Men in both countries were more likely to report use of alcohol and illicit substances than women. Generally speaking, a greater proportion of respondents in both countries 18 years of age or older reported use of alcohol for all three measures than younger respondents; and a greater proportion of respondents between the ages of 18 and 34 years reported use of illicit substances during lifetime and past year than any other age group.^ Additional substantive research investigating population-based samples and at-risk subgroups is needed to understand the underlying mechanisms of these associations. Further development of cross-culturally meaningful survey methods is warranted to validate comparisons of substance use across countries and societies. ^

THE RELATIONSHIP BETWEEN OBESITY AND PSYCHOLOGICAL GENERAL WELL-BEING IN UNITED STATES WOMEN

While clinical studies have shown a negative relationship between obesity and mental health in women, population studies have not shown a consistent association. However, many of these studies can be criticized regarding fatness level criteria, lack of control variables, and validity of the psychological variables.^ The purpose of this research was to elucidate the relationship between fatness level and mental health in United States women using data from the First National Health and Nutrition Examination Survey (NHANES I), which was conducted on a national probability sample from 1971 to 1974. Mental health was measured by the General Well-Being Schedule (GWB), and fatness level was determined by the sum of the triceps and subscapular skinfolds. Women were categorized as lean (15th percentile or less), normal (16th to 84th percentiles), or obese (85th percentile or greater).^ A conceptual framework was developed which identified the variables of age, race, marital status, socioeconomic status (education), employment status, number of births, physical health, weight history, and perception of body image as important to the fatness level-GWB relationship. Multiple regression analyses were performed separately for whites and blacks with GWB as the response variable, and fatness level, age, education, employment status, number of births, marital status, and health perception as predictor variables. In addition, 2- and 3-way interaction terms for leanness, obesity and age were included as predictor variables. Variables related to weight history and perception of body image were not collected in NHANES I, and thus were not included in this study.^ The results indicated that obesity was a statistically significant predictor of lower GWB in white women even when the other predictor variables were controlled. The full regression model identified the young, more educated, obese female as a subgroup with lower GWB, especially in blacks. These findings were not consistent with the previous non-clinical studies which found that obesity was associated with better mental health. The social stigma of being obese and the preoccupation of women with being lean may have contributed to the lower GWB in these women. ^

Cutaneous malignant melanoma: A study of skin cancer in the United States from 1973--1997

Cutaneous malignant melanoma (CMM) is the cancer of the melanocytes, the cells that produce the pigment melanin, and is an aggressive skin cancer that is most prevalent in the white population. Although most cases of malignant melanoma are white, black and other non-white populations also develop this disease. However, the etiologic factors involved in the development of melanoma in these lower-risk populations are not well known. Generally, survival rates of malignant melanoma have been found to be lower in blacks than for whites with similar stage of disease at diagnosis. ^ This study presents an analysis of the differences in survival between black and white cases with malignant melanoma of the skin as the only or first primary cancer, found in the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) cancer registry from 1973 to 1997. A total of 54,193 cases of CMM were diagnosed in black and white patients between 1973 and 1997. Black patients tended to be older, with a mean age of 64.46 years, compared to 53.14 years for white patients. Eighty-nine percent of patients were diagnosed with CMM as the only cancer. (Abstract shortened by UMI.)^

The status of genetically modified foods internationally and in the United States

Biotechnology refers to the broad set of techniques that allow genetic manipulation of organisms. The techniques of biotechnology have broad implications for many industries, however it promises the greatest innovations in the production of products regulated by the Food and Drug Administration (FDA). Like many other powerful new technologies, biotechnology may carry risks as well as benefits. Several of its applications have engendered fervent emotional reactions and raised serious ethical concerns, especially internationally. ^ First, in my paper I discuss the historical and technical background of biotechnology. Second, I examine the development of biotechnology in Europe, the citizens' response to genetically modified (“GM”) foods and the governments' response. Third, I examine the regulation of bioengineered products and foods in the United States. ^ In conclusion, there are various problems with the current status of regulation of GM foods in the United States. These are four basic flaws: (1) the Coordinated Framework allows for too much jurisdictional overlap of biotechnological foods, (2) GM foods are considered GRAS and consequently, are placed on the market without pre-market approval, (3) federal mandatory labeling of GM foods cannot occur until the question of whether or not nondisclosure of a genetic engineering production processes is misleading or material information and (4) an independent state-labeling scheme of GM foods will most likely impede interstate commerce. ^

Second, do less harm: The state of states' medical error reporting programs

Statement of the problem and public health significance. Hospitals were designed to be a safe haven and respite from disease and illness. However, a large body of evidence points to preventable errors in hospitals as the eighth leading cause of death among Americans. Twelve percent of Americans, or over 33.8 million people, are hospitalized each year. This population represents a significant portion of at risk citizens exposed to hospital medical errors. Since the number of annual deaths due to hospital medical errors is estimated to exceed 44,000, the magnitude of this tragedy makes it a significant public health problem. ^ Specific aims. The specific aims of this study were threefold. First, this study aimed to analyze the state of the states' mandatory hospital medical error reporting six years after the release of the influential IOM report, "To Err is Human." The second aim was to identify barriers to reporting of medical errors by hospital personnel. The third aim was to identify hospital safety measures implemented to reduce medical errors and enhance patient safety. ^ Methods. A descriptive, longitudinal, retrospective design was used to address the first stated objective. The study data came from the twenty-one states with mandatory hospital reporting programs which report aggregate hospital error data that is accessible to the public by way of states' websites. The data analysis included calculations of expected number of medical errors for each state according to IOM rates. Where possible, a comparison was made between state reported data and the calculated IOM expected number of errors. A literature review was performed to achieve the second study aim, identifying barriers to reporting medical errors. The final aim was accomplished by telephone interviews of principal patient safety/quality officers from five Texas hospitals with more than 700 beds. ^ Results. The state medical error data suggests vast underreporting of hospital medical errors to the states. The telephone interviews suggest that hospitals are working at reducing medical errors and creating safer environments for patients. The literature review suggests the underreporting of medical errors at the state level stems from underreporting of errors at the delivery level. ^